Project Summary The HIV Eradication Scientific Working Group (SWG) was created to directly address one of the high priority research areas of the OAR: ?to develop novel approaches and strategies to eliminate viral reservoirs that could lead toward a cure or lifelong remission of HIV infection?. Despite the major success of combination antiretroviral therapy (cART) in suppressing viral replication and preventing disease progression, HIV-1 infection persists in a latent reservoir, composed primarily of a long-lived population of resting memory CD4+ T cells. These latently infected cells harbor replication competent HIV-1 DNA, therefore the elimination of the latent viral reservoir is essential to eradicating HIV-1 infection. Major challenges to the elimination of the reservoir are the lack of: (i) robust, sensitive and reliable assays to accurately measure and localize the reservoir of replication-competent proviruses; (ii) basic understanding of the mechanisms that lead to latent reservoirs; and (iii) reliable methods to reactivate latent cells and to target them for killing. The HIV Eradication SWG was formed to bring together outstanding investigators who have not previously collaborated: (i) from within the three ERC-CFAR institutions; (ii) from other New York City institutions, including Columbia University Medical Center, New York University, and Icahn School of Medicine at Mount Sinai; and (iii) non-AIDS experts from other fields, to develop a multi-pronged approach to synergize basic, translational, and clinical efforts targeted towards HIV eradication. This SWG will leverage the clinical samples, assays and technologies available through the laboratory and clinical cores of the ERC-CFAR to drive research efforts to eradicate HIV-1 infection and thereby prevent new infections. This SWG aims to: (i) foster collaborations among SWG members and affiliates to focus on the molecular mechanisms of latency and on the development and evaluation of novel and alternate modalities for HIV Cure; (ii) use the ERC-CFAR cores to support and recruit experts from non-HIV/AIDS areas and Early Stage Investigators to develop innovative technologies to quantify and eradicate HIV infection; and (iii) To obtain funding for research projects that are developed through new collaborations and ideas formed in the SWG to increase our understanding of the underlying mechanisms that generate and maintain latent reservoirs and to develop reliable methods to reactivate latent cells and to target them for killing.